Art as research, research as art?

Two stories in the past two weeks have got me thinking more about what is an ongoing and fascinating debate between those in the research ethics world and the art world. When is art research? And when is research art? I certainly don't claim to have a definitive answer nor, arguably, do the Canadian federal guidelines. Many people engaged in the review of human participant research across Canada are thinking and talking about this. The discussions usually revolve around the difficulty of defining just what is research and what is art and trying to draw what is often an artificial line between the two.

Many artists, obviously, are deeply concerned with the way that the public reacts to their work, whether it's visual, auditory or highly interactive, like Cildo Meireles' work, as described below in The New York Times and pictured above. This amounts to a kind of research as in essence, visual artists want to know why someone is compelled to gaze at a particular painting or photograph or why a specific image compels someone more than another. For many artists, the visceral, emotional or lasting emotional reactions of others is a deeply important component of the evolution of their work and their development as an artist. But is the exploration of how people experience art research? Some would say, yes.

Institutions like the Ontario College of Art and Design in Toronto have newly formed research ethics boards to review research projects. But one of the most important first — and likely, ongoing — challenges will be to decide what's art and what's research.

The point of having an ethics review board is to protect human participants and to ensure a fair balance between risk and benefit in research.

Sometimes, art too, involves risk.

Here are two stories that highlight, at least to some degree, that there may be risks involved in art and the experience of appreciating art.

From CBC News: Artist fined over inflatable artwork that killed 2

A British artist whose inflatable artwork blew away killing two women who were inside has been fined the equivalent of $17,800 after being convicted of offences under the Health and Safety Act...In July 2006, a sculpture the size of a football field that was anchored in a County Durham park broke free from its moorings, carrying several people with it. Two women died and 13 people were injured, including a three-year-old who fell from the sculpture and was saved by a passing doctor.

From The New York Times: In Barcelona, Conceptual Art by Cildo Meireles

After all, how many contemporary art exhibitions require visitors to sign not one but two waivers releasing the museum from any responsibility for personal injury? Several of the artist’s installations, which fall into the broad category of conceptual art, call on the visitor to participate in the artistic experience. In the end, there is likely little risk of harm but considerable likelihood for enjoyment and perhaps even a bit of revelation. Assuming one is properly shod, walking on a sea of broken glass produces a crackling concert of sounds as the seemingly endless layers of glass bits crunch and snap under foot. It is equally unsettling to walk into a darkened room and instantly recognize the distinct odor of natural gas permeating the air, as in the work “Volatile” (1980-1994). The fake gas smell however fails to stop virtually anyone from continuing further into the room, where those who are willing can have some fun trying to move around in a separate chamber that has been packed ankle deep with talcum powder (rubber boots and masks are provided).

Having risk involved in viewing or experiencing art doesn't make it research or in need of a research ethics review. Certainly not. But it changes the way we think about the experience of taking in an exhibit if we are asked to sign a consent form outlining risk. It does raise issues of oversight — who has ensured that there is enough glass on the floor to make the exhibit engaging versus cutting through a canvas running shoe? In some ways, many complain that we live in a far too insulated and regulated world and that risk — or what is left of risk — is exaggerated and overemphasized. In many cases, I'd agree. (Furthermore, the notion of risk is seen very differently by those in different worlds. In the art world, 'risk-taking' may be seen as innovative and encouraged but that's something far different than exposing people to physical harm). However, in the first case above, the safety of the exhibit and potential physical risk to visitors was clearly much more than what anyone assessed.

Arugably, how we experience the world is what most social science researchers, regardless of their discipline, want to observe and better understand. How we experience art is one way of how we interact with, experience and interpret the world around us. Does the examination or study of such reactions turn artists into researchers? Does it make a difference if there is some kind of potential risk or possible harm involved? I think the only way we'll move forward here is not by seeking definitive "one size fits all" kind of answers but rather by openly sharing experiences and subsequent decisions (ethics review boards and artists together) and building, in essence, a shared and iterative body of cases based on real-life decisions to which those seeking some guidance can refer.

Here is a link to the SSWHC document, prepared for the Canadian Panel on Research Ethics (PRE) entitled: Research Involving Creative Practices: A Chapter for Inclusion in the TCPS

Addicts (And Other Vulnerable Populations)

From the Washington Examiner: Federal programs gave addicts street drugs:

The federal government is giving crack and powder cocaine, morphine, and other hard-core drugs to taxpayer-funded researchers for testing on addicts, The Examiner has learned.
For decades, the government has authorized, funded and lobbied for studies in which otherwise illegal drugs were given to addicts in cities such as Washington, Bethesda, Baltimore, New York, Minneapolis and San Antonio. The studies continue today and have an array of aims, from documenting the ways cocaine warps the brain to the intensity of pain from morphine withdrawal.

Just 2 quick points:

1) Those versed in Research Ethics already understand this point, but this story highlights the conflict inherent in studying vulnerable populations: members of vulnerable populations can make for very good research subjects, precisely because they are vulnerable and the need to understand their problems is great. But their very vulnerability also makes studying them ethically treacherous. In many cases — not just in the case of addicts — their vulnerability tends to reduce our confidence in their ability to give valid consent.

2) The Examiner article seems somewhat slanted. It feels as if the reporter is defending otherwise-defenseless addicts against predatory researchers, which might just be unfair. And the story really provides too little information to figure out whether there's anything inappropriate going on, here. But I think it's useful to consider what the role of the media is. Yes, members of the news media are ethically obligated to be fair. But when in doubt, they ought to side with the weak & disadvantaged. I'm not necessarily rendering judgment on whether this particular story is fair & balanced. The point is simply that researchers & the institutions that fund them ought to expect, if not welcome, such scrutiny, and regard it as part of their public obligation to be ready to explain and defend their research on such vulnerable populations.

Guest post Friday on the Social Science Research News Blog

Today I wrote a guest blog entry for the Social Science Research News Blog. Every Friday, they ask a guest blogger to author the post. It's a great blog to follow for anyone interested in social science research.

Here is how the blog is described: "Social Science Research News is a collection of news and scholarly works on the science - and art - of publishing and research in the social sciences. Each post will conclude with a call for your comments - share your experiences with the topic."

For my guest post, I've written a short and quite general piece on the issue of coercion in social science research. Have a read and make sure that while you're there, you check out the rest of the blog or sign up to follow them on Twitter.

Here's the link directly to today's blog entry: Guest Post Friday - Coercion in Research.

Distorting the story? The reporting of research in the media.

Simon Baron-Cohen, a prominent autism researcher in the UK just published an excellent commentary in the New Scientist about the responsibilities of journalists who cover scientific research stories.

Here is the link to the commentary: Media distortion damages both science and journalism

When media reports state that scientist X of Y university has discovered that A is linked to B, we ought to be able to trust them. Sadly, as many researchers know, we can't.

This has three serious consequences. For starters, every time the media misreports science, it chips away at the credibility of both enterprises. Misreporting can also engender panic, as people start to fear the adverse consequences of the supposed new link between A and B. Lastly, there can be a damaging effect on researchers' behaviour. Funding agencies and science institutions rightly encourage scientists to communicate with the media, to keep the public informed about their research and so foster trust. If their work is misrepresented, they may withdraw into the lab rather than risk having to spend hours setting the record straight.

Baron-Cohen goes on to state that in his field — autism research — which he calls "sensitive", there have been a number of tragic distortions of research findings by the media. The most notable one is the Andrew Wakefield case, in which research findings, and the subsequent reporting of these findings linking autism to the MMR vaccine, led to marked (and persistent) decreases in immunizations rates across the UK. Baron-Cohen also describes his own challenges with having his research findings distorted by journalists and highlights how something as seemingly benign as an inaccurate headline, subtitle or picture caption can take on a life of its own, even when the facts are presented accurately in an accompanying story.

The final two paragraphs of the commentary really hit home. Baron-Cohen notes that the reason why we have ethics review boards is to regulate scientists and science as, realistically, harm can result to the public in the conduct of research. He asks if we shouldn't also consider some kind of separate regulation of journalists prior to allowing the publication of stories on scientific research findings in the mass media. This wouldn't be the jurisdiction of an ethics review board, certainly, but some other kind of body. Right now, we do ask researchers to consider how their results will be disseminated — but mostly in order to try to make sure that researchers inform participants about how the results will be used and reported. Ethics review boards certainly can't ensure that the research findings are reported properly. This should be the responsibility of the individual researchers. But as the commentary describes, even the most responsible researcher who presents the most accurate account of research findings to a knowledgeable journalist can end up with a headline or picture caption that takes the story in a whole new, and inaccurate, direction.

Inaccurate or inflated reporting of research findings, exaggerating the importance of research outcomes or representing correlation as causation are all things that can happen in media reports of scientific research. Arguably, this can cause real harm. While journalists do have professional codes of ethics, it is understandably tempting to publish a more sensational headline that makes the front page, instead of the moderate, safe and perhaps more accurate headline that will be passed over by most readers. As Baron-Cohen notes, though, the fallout from this can be tragic for all involved.

Thank you to BG for pointing me to this story.

The Oncologist Takes Action on Ghost Writers

The uninitiated could be forgiven for assuming, upon seeing a research article with a prominent physician-researcher's name at the top, published in a respected medical journal, that that physician-researcher had actually written the article. But that's not always the case. Articles are sometimes written, in whole or in part, by 'ghost writers,' whose expertise is not always known and whose loyalties do not necessarily lie with the public interest. Medical journals — conscientious ones — are justifiably concerned about the practice. Here's a prominent journal taking action on the issue.

From Bruce A. Chabner, M.D., Editor-in-Chief of The Oncologist: Ghost Writers in the Sky

Lately The Oncologist has received a spate of articles written with the assistance of paid medical writers, "ghost" writers if you will, who are not recognized in the authorship byline, but who contribute in variable degrees to the final product. These writers are usually recorded in an acknowledgment and their support from a pharmaceutical company may be identified, but their role in producing the intellectual product is often unclear. In some cases, once we have asked for clarification of a writer's role, or during the course of revising the manuscript, it becomes apparent that his or her role is predominant. We have seen revisions that have been made and transmitted by ghost writers, and not the authors. Indeed, the role of the named authors at times seems incidental, as the ghost writers have taken over the project.

So, The Oncologist has instituted a new policy. The policy reads, in part:

For the monthly issues of The Oncologist, we will accept papers for review only if the article was written, endorsed, and proffered for publication by the authors identified in the byline. The authors must attest that this is their creation for which they take full responsibility. If a paid writer participates in the writing of the article, the nature of that assistance must be clearly identified in the acknowledgment, and the source of support for that writer must also be stated. If the support for the ghost writer comes directly or indirectly from a party with a commercial interest in the content, and the hired writer has had the primary responsibility for writing and submitting the paper, but is not identified as an author, we will not accept the article for review or publication. If a company employee participates in designing and executing a clinical trial and participates in the writing of a paper, their authorship is not only acceptable, it is necessary. We will correspond with authors of the paper, but not with hired writers who are not recorded as authors. We will also not accept review articles for publication in our regular monthly issues if they are written by a ghost writer paid directly or indirectly by a drug sponsor.

I don't know whether other journals have such policies. But it will be interesting to see if those that don't have them end up following suit. And if they don't...why not?

Personal relationships, conflict of interest and ethics

The Pittsburgh-Tribune Review reported recently on The University of Pittsburgh Medical Center's April 1st ban on the delivery of drug samples to physicians and and offices by drug reps.

Here is the story from the Pittsburgh-Tribune Review: UPMC to stop reps' delivery of drug samples

The policy is meant to eliminate perceived or actual conflicts of interest between UPMC providers and drug companies. UPMC banned gifts and meals to hospital personnel by health care companies more than a year ago.

"There is a concern that personal relationships can influence decision-making," said Dr. Barbara E. Barnes, associate vice chancellor of the University of Pittsburgh.

A computerized system run by a private firm, MedManage Systems, will replace sales reps' visits. It allows doctors to order samples that would be shipped to physicians' offices.

So, to be clear, this isn't about the ethics of providing free drug samples. Nor is it about drug swag or free lunches. This is about relationships between people, specifically drug reps and physicians. In this context, the term "relationship" doesn't have to imply a friendship or a sexual relationship. It merely refers to the establishment of an ongoing connection. The Pittsburgh ban doesn't end the actual delivery of drug samples and vouchers to physicians' offices. Nor does it end the delivery of information about the drugs to physicians' offices. It only ends the personal delivery of any of this by drug reps.

Drug reps are, from my own clinical experience, usually very smart, young professionals who not only know a lot about the drugs and products that they are promoting, but probably a heck of a lot about human interaction, how to connect effectively with people and most of all, how to sell their products. They work hard at developing good relationships with physicians and their office staff and promote the product that they represent, through personal interaction, free samples and a high level of friendly service.

So what's the point here and where is the connection to research ethics? Well, clearly, in all contexts, relationships matter. Relationships between people are an obvious source of conflict of interest. While often the source of conflicts of interest in research lies in personal gain — for example, a researcher who stands to make a profit from the research or get an academic promotion — the source could instead be a personal relationship and how that relationship and the obligations implied by such a relationship might alter the researcher's ability to make a sound decision in a professional context.

In the present case, The University of Pittsburgh Medical Center's ban on drug reps implies concern about the effect of personal relationships on prescribing practices. Arguably, personal relationships might also influence other kinds of related activities including research and the reporting of research findings. While most ethics review boards ask researchers to note any real or potential conflicts of interest, most researchers report things like financial interests, or having a stake in a patent or copyright. I doubt that many Board members have read a research ethics application listing a personal relationship that might have a potential effect on how a researcher is able to conduct research or report findings. It's clear that the University of Pittsburgh is taking an unparalleled first step in acknowledging that personal relationships and subsequent obligations may well alter good judgment and sound practices.

Update: Ethics on the chopping block

Last week, we reported the proposed closure of the ethics program at the University of Tennessee along with the elimination of the Bioethics Council of New Zealand.

A well-informed reader got in touch with us to tell us some further details about the University of Tennessee closure, which we'll summarize here.

It seems that the UT College of Medicine, in which the Ethics department is housed, has proposed a formula to establish which programs should continue and which ones should be cut. The elements of the formula involve student hours taught along with research revenue generated. If the department also brings in clinical revenue, it's looked upon even more favourably.

According to this reader, the plan for the cuts sends two clear, and arguably problematic, messages.

The first message is that only money matters in terms of measuring importance and productivity of persons and academic units. Individual faculty members must generate research dollars and clinical dollars in order to be considered valuable. Individual faculty members — who are, at most academic institutions, already under pressure to bring in research funds — will be under even more pressure at UT to generate funds to ensure that their whole unit won’t close because of their individual “lack of productivity”.

The second message is that rules don’t matter. The proposed closure and the resultant cuts to ethics education for medical students potentially violate national accreditation standards for medical education, according to our reader. The message here is that rules don’t matter — even if they are nationally accepted rules about how future physicians should be educated.

I think that these cuts, as the reader has outlined them, sends yet another message — that ethics doesn’t matter. These medical students are future clinicians and researchers. Having clinical knowledge and expertise alone isn’t sufficient in order to be a good researcher. In fact, clinical knowledge and expertise aren’t enough to be a good clinician, either. Having knowledge about ethics, and opportunities to apply this knowledge in both clinical and research contexts, is just as fundamental as learning how to insert a 'central line' or how to analyze a dataset.

AstraZeneca: 'Smoke & Mirrors' Hiding Seroquel Flaws

From The Washington Post: A Silenced Drug Study Creates An Uproar

The study would come to be called "cursed," but it started out just as Study 15.

It was a long-term trial of the antipsychotic drug Seroquel. The common wisdom in psychiatric circles was that newer drugs were far better than older drugs, but Study 15's results suggested otherwise.

As a result, newly unearthed documents show, Study 15 suffered the same fate as many industry-sponsored trials that yield data drugmakers don't like: It got buried. It took eight years before a taxpayer-funded study rediscovered what Study 15 had found -- and raised serious concerns about an entire new class of expensive drugs.

Study 15 was silenced in 1997, the same year Seroquel was approved by the Food and Drug Administration to treat schizophrenia. The drug went on to be prescribed to hundreds of thousands of patients around the world and has earned billions for London-based AstraZeneca International -- including nearly $12 billion in the past three years....

A recent (informal) survey at the Pharma Marketing Blog asked "What's the Cause of the Drug Industry's Bad Reputation?" The results showed the view of industry to be seriously out of step with that of the public. The blog also quoted one pharma exec as asking "How in the hell do we have such a bad reputation?" Hmm, yes, how indeed.

Clinical Trials in India: The View From India

Here's another story about clinical trials being conducted overseas. Except this time, I can't refer to it as "outsourcing" (sending research out to another country) because here the story is being told from the point of view of the country bringing the research in.

From the Indian daily newspaper, Mid-Day: Study finds Illegal clinical trials in India:

Three MNC drug firms have conducted illegal clinical trials in India, says an investigation by Mumbai-based Centre for Studies in Ethics and Rights.

Drug major GlaxoSmithKline (GSK) has unethically tested a breast cancer drug on poor patients in India for approval for new drugs in the Europe Union, said a study.

The firm had tested lapatinib on patients flouting Indian Council of Medical Research's (ICMR) ethical guidelines.

This trial required seriously ill patients who had not received treatment for their condition. GSK took advantage of the "vulnerable position" of breast cancer patients, said the study released last month....

The other two companies named in the story are Astrazenica and Johnson & Johnson (both accused of inappropriately using placebos in trials on patients with serious psychiatric conditions).

Now, it's worth noting that, contrary to the headline and the story's opening sentence, there's no clear evidence of any illegal activity here. The research practices detailed certainly look highly unethical, but there's nothing clearly criminal (though that doesn't rule out civil liability of course). The word "illegal" might be being used because of a misunderstanding of the legal weight of the Declaration of Helsinki, which is mentioned in the story's closing paragraphs. The Declaration isn't legally binding; it's force is moral, not legal. That's not to minimize its significance, or to downplay the gravity of practices that violate it; but the distinction is typically thought an important one. But as this story perhaps demonstrates, from a certain perspective — perhaps the perspective of a commentator inside a developing nation — the difference might not matter much at all.

(Here's the website for the Centre for Studies in Ethics and Rights; unfortunately, their "Studies" page seems to be password-protected.)

Private IRB subject of sting operation

University-based research is overseen by university ethics boards. Hospital-based research is reviewed by hospital ethics review boards. But research conducted by private companies is typically overseen by private ethics boards. Some people worry about how careful private boards will be. Here's a story about that.

From the NY Times: Testing Firm Finds Itself Being Tested

Like other federal undercover operations, this one had the usual trappings, like a company whose address turned out to be a P.O. box in a strip shopping mall and a businessman whose credentials proved fraudulent.

But the investigation had an unusual focus: determining whether companies that are paid to oversee the safety of patients in clinical studies of drugs and medical devices do their job. The inquiry came to light this week when one of its targets, a Colorado company, exposed it — via news release.

The company, Coast Independent Review Board, said it had been duped by federal officials last year when it agreed to oversee a study of Adhesiabloc, a product designed to reduce scar tissue after surgery.

As it turns out, there is no such product....

The New York Times article was highly critical of Coast for not "checking" into the investigators' claims of affiliations and qualifications or even the location of the study, which, upon investigation, was actually a store in a strip mall. As it turned out, the only revisions requested in the protocol were on the consent form and someone from Coast IRB actually spoke with a person who represented himself as a researcher affiliated with the study and who agreed to make the changes prior to approval.

This story isn't as much about private IRBs, though, as it is about what an ethics review board should be asked to do. And whether or not we should hold private ethics review boards to higher standards.

Many ethics review boards — private or not — accept protocol submissions, send them out to reviewers, get the reviews completed, discuss the requested changes and send the protocol back to the researcher, who then makes the required changes, resubmits. At some point in this process, the protocol gets approved. But this entire process can be done by email or by hard copies of protocols delivered to assistants by couriers. In other words, most ethics boards never meet most of the researchers whose work they are reviewing. At a small University or hospital, people know each other. Names on research ethics protocols are familiar, well known. But take any large hospital or University and it is guaranteed that many protocols will come before the Board with unknown names, external researchers who no one has ever met, along with companies and sponsors that are unfamiliar. Ethics review board members simply can't meet every researcher, visit their study lab or clinic or check professional associations to ensure that researchers are in fact who and what they say they are.

Is it a case of blind trust? Or a case of "what we don't know won't hurt us"? I think neither. No already overworked ethics review board can be expected to be checking up on these sorts of things with every protocol that comes to them. The House Subcommittee that led the sting was checking up on the wrong thing. Coast did its due diligence. It ensured that the study was ethically sound. That's the job that they — like any other ethics review board — are mandated to do. Could they have done more? Absolutely, yes. But does every other ethics review board — private or not — always do more? Almost never.

Here, FYI, is Coast IRB's website.

Update: Seroquel, Sex, Conflict of Interest

We blogged last month about Seroquel, Sex, and Conflict of Interest, which involved the AstraZeneca exec who oversaw research on the antipsychotic drug trading, well, sexual favours for favourable treatment of the drug by a researcher and a study writer. We pointed out that it was an interesting case (all titillation aside) because it was a conflict-of-interest story that didn't involve money.

Here's the latest, from Bnet: AstraZeneca's Seroquel Research Director Confessed to Sex-for-Studies Affairs

Former AstraZeneca U.S. medical director for Seroquel Wayne MacFadden confessed his multiple sexual affairs, and his offer of drugs to one of the women he was sleeping with, to lawyers in December 2007.

The confessions include descriptions of sex in hotel rooms paid for by AZ, illicit distribution of Vicodin, and a kinky relationship in which one of his colleagues asked to be “punished” for looking at a study that had negative results for Seroquel.
....
He made the confession to the lawyers — who are suing AstraZeneca for allegedly failing to warn patients that side effects of the drug include significant weight gain and diabetes — as part of a deposition prior to the current litigation going on in Florida.

The Bnet article also includes snippets from various depositions, including juicy/sordid bits like this exchange between MacFadden and a lawyer:

Q: Sir, you’re using sex to try to get trade secrets out of Bristol-Myers Squibb to benefit AstraZeneca. That’s not only unethical, that’s illegal, isn’t it?
A: I don’t know that.
Q: You were pumping her for information, correct? I withdraw that question. You were trying to get information out of her?
A: It appears that I asked her for information.

That's not how research is supposed to be done. That's not how innovation is supposed to go. Then again, it's a system full of humans. That's not a justification. Just an observation.

Who should decide how we spend research dollars?

It is turning out to be a week of contrasts. While the US is opening up funding opportunities for stem cell research, news of cuts in neuroscience research are being reported here in Canada.

This story appears in yesterday's Globe and Mail: Team Grants Axed: Neuroscientists fear brain drain as crucial funding disappears

According to the story, there has been a five percent cut across all three federal granting councils: the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council (NSERC) and the Social Sciences and Humanities Research Council (SSHRC). Along with other cuts, the elimination of the grant highlighted in this story — a neuroscience Team Grant already awarded through CIHR — will save the agency an estimated 34.6 million dollars over three years.

"The cuts exacerbated a funding crunch that has left many senior researchers scrambling to find money to continue their experiments and wondering how Canada will keep its top talent - and attract the best young scientists - at a time when the United States is pouring billions into science. The team grants were axed as part of the $147.9-million in cuts over three years to the CIHR and the two other granting councils that finance research at universities across the country."

Who should be making decisions about how research funding is spent (or taken away)? Certainly in the US, the increased availability of funding for stem cell research has not been met with universal rejoicing. Many who oppose this kind of research are wondering why their opinions are not being heard or their cautions heeded. Some would say, they certainly had a chance in November to cast their vote, but that assumes it was a single-issue election, which it wasn't . This story highlights the same kind of thing and raises the same types of concerns (about decision-making), except it isn't about giving more money, it's about taking it away.

Priority setting, done thoughtfully, is an important part of sustaining any kind of program or institution. Difficult, even tragic priority setting decisions like this one, about spending more — or less — money on research should involve transparent processes involving key stakeholders. But whom? Scientists shouldn't be the only ones at the decision-making table. However, at the same time, the table should include more than politicians and policy makers.

It's true, the three funding bodies in Canada have thorough peer review processes to make decisions about how funds are allocated. But are subsequent cuts to programs peer-reviewed? Who gets a say in what stays and what gets axed? Are there people included in the process who have an idea of the "local" situation and fallout from the decisions being made, i.e. what will happen to the research team, program, participants and patients? And finally, is there consideration of the broader societal implications of such decisions — will this really result in a "brain drain" of good researchers and scientists to other institutions or, in this case, other countries?

Falsifying Data: Anesthesiology Research May Have Found its Own Bernie Madoff

You all know who Bernie Madoff is. He's the guy who pulled off the biggest financial scam in history. Madoff's scam wasn't just big. It was enormous. Mind-boggling. How, everyone asked, did he pull it off? And beyond that, what made him think he could get away with it?

Now, it looks like the field of Anesthesiology research may have its own Bernie Madoff, in the person of one Scott S Reuben, MD.

The story comes from Anesthesiology News, and reported repeated the Pharmola.com website: Fraud Case Rocks Anesthesiology Community

In what experts are calling one of the largest known cases of academic misconduct, a leading anesthesiology researcher has been accused of falsifying data and other fraud in potentially dozens of published studies.

Scott S. Reuben, MD, of Baystate Medical Center in Springfield, Mass., a pioneer in the area of multimodal analgesia, is said to have fabricated his results in at least 21, and perhaps many more, articles dating back to 1996. The confirmed articles were published in Anesthesiology, Anesthesia and Analgesia, the Journal of Clinical Anesthesia and other titles, which have retracted the papers or will soon do so, according to people familiar with the scandal....

How on earth....? Well, details are still foggy. But the story quotes my friend, Josephine Johnston, who works at the Hastings Center:

What’s particularly surprising given the dimensions of the case, Ms. Johnston said, is that Dr. Reuben’s research managed to raise no alarms among peer reviewers. However, she added, “the peer review system can only do so much. Trust is a major component of the academic world. It’s backed up by the implication that your reputation will be destroyed if you violate that trust.”

(The original Anesthesiology News story, here, requires registration.)

Obama, science, politics and ethics.

The world watched today as President Barack Obama, many noted, "lifted the ban on stem cell research" in the USA. While most news stories noted that scientists were applauding and thrilled, let's be honest, many of the public were torn somewhere between joining in the applause and scratching their heads. They're pretty sure that it means more research can be done using stem cells, but many simply have no idea what's been restricted and what kinds of restrictions have been lifted. Even the highly enthusiastic journalists are reporting "huge exciting changes in policy" and "new frontiers in science possible"! Except a few. Like one journalist who offered a perspective on today's story, clearly outlining what kinds of changes will result from Obama's actions and just what this all means, with a bit of history on stem cell research funding thrown in for context.

Here is the story from The New York Times: Rethink stem cells? Science already has.

Restrictions on embryonic stem cell research originated with Congress, which, each year since in 1996, has forbidden the use of federal financing for any experiment in which a human embryo is destroyed. This includes the derivation of human stem cell lines from surplus fertility clinic embryos, first achieved by Dr. James Thomson of the University of Wisconsin in 1998. President Clinton contemplated but never implemented a policy that would have allowed N.I.H.-financed researchers to study human embryonic stem cells derived by others. Research was able to begin only in August 2001, when President Bush, seeking a different way around the Congressional restriction, said researchers could use any lines established before that date....Mr. Obama has put the proposed Clinton policy into effect, but Congressional restrictions remain. Researchers are still forbidden to use federal financing to derive new human embryonic stem cell lines. They will, however, be allowed to do research on new stem cell lines grown in a privately financed lab.

This story has been looming all weekend and many have been anxiously discussing, rejoicing or blogging about it. But most people that I talk to in the street or the hallway, don't really understand it. And I think that's a very important point.

Okay, here's a very small amount of (very) basic science and then some history. Stem cell research can be done on two kinds of cells: Adult stem cells and embryonic stem cells. Adult stem cells come from adults and no one needs to be hurt or injured. There have never been restrictions in the USA on the use of adult stem cells. These cells are, however, limited in their usefulness. Embryonic stem cells, on the other hand, come from fertilized embryos that, by removal of the stem cells, destroys the embryo. These cells have a wider range of possibilities for research than adult stem cells. In the US, there have always been some restrictions on the use of embryonic stem cells, dating back to 1996 when the Dickey-Wicker amendment was passed by Congress, which prohibited the use of federal funding to create or destroy embryos in order to generate or collect stem cells for research. This amendment has been reiterated by Congress, year after year and the prohibition stayed in place. President Bush, in 2001, allowed a small number of already existing stem cell lines to be used in research with federal funding, but these cell lines were ones already in existence before that time. So only those cell lines approved by Bush were allowed to be tested using federal research funds.

But that doesn't mean that there wasn't any testing ongoing on other embryonic stem cell lines. What it meant was that if you were a scientist who wanted to use unapproved stem cells, you had to find your own funding and labs as well as ensure that no federal funding was used in conducting the reseach. Expensive, time consuming and laborious, even for the most dedicated researchers.

Now those same researchers who want to use these kinds of embryonic stem cell lines can apply for federal funding through agencies like the National Institutes of Health.

Okay, but Obama didn't do one thing. He didn't alter the Dickey-Wicker amendment, leaving it instead up to Congress, which has, year after year, upheld this without much discussion or argument. So, federal funding still cannot be used to create or destroy embryos for research purposes. Again, they can still be made and are being made, but only in private labs using private funding.

So essentially, Obama has really only moved the playing pieces around the board a little bit. Yes, he's allowed the pieces a bit more freedom to move, but there are still clear restrictions on where the funds for research can come from and how they can be used. Simply put, this is less about what kinds of research gets done and more about who pays for it. Researchers are now able to use federal funds — like NIH funds — to use stem cells derived by others in private labs using private funding but because of the Dickey-Wicker amendment, they still can't really "grow their own". I think it's important to note that, really, Obama isn't allowing more kinds of stem cell research to be done, he is facilitating it by allowing access to federal funding. It's being done already and has been throughout the Bush presidency, just not with tax payers' money.

There is a great deal of hype around the so called "reversal" of Bush's decision today. I think that it's important that journalists and scientists be very clear about the details of what is going on for the public, on this issue and many others. Research ethics boards struggle with this every day: How to help researchers communicate often complex or highly scientific research to the public who have a right to be informed. It's important that the public understand science and the impact that scientific research has on the world around us, especially with a highly sensitive issue, like this one, that triggers strong emotional reactions and moral convictions. When science mixes with politics, well, it can become even more obscure.

Research Integrity: Catching Plagiarism

Would you expect to find plagiarism in the published, peer-reviewed work of health researchers?

Academics reading this may already have heard of turnitin.com, a service that helps professors find out if their students have plagiarized all or parts of their essays.

A new tool called eTBLAST does something similar, but shifts the focus onto the professors themselves. It's designed to find significant similarities between scientific papers. Here's the story: Authors, Journal Editors Respond to Possible Cases of Plagiarism Identified by Analysis

In the past two years, UT Southwestern researchers have used a computer-based text-searching tool they developed, called eTBLAST, to analyze millions of abstracts randomly selected from Medline, one of the largest databases of biomedical research articles. They turned up nearly 70,000 highly similar citations.

Their subsequent analysis of a small sampling of these, including human inspection of the articles in question, revealed 207 pairs of articles with signs of potential plagiarism.

(The study is presented here in Science — SCIENTIFIC INTEGRITY: Responding to Possible Plagiarism — but it requires subscription.)

Ethics on the chopping block

Two related stories came to my attention this week. Reading the first one, I was worried. But when I came across the second story, I thought, this needs to be talked about! In two places, both affected by the now globally worrisome economy, strict budget cuts are being made. And the first thing on the chopping block? Ethics.

The University of Tenneessee is considering closing down The Department of Human Values and Ethics in the College of Medicine along with a number of other science and medicine programs. Here's the story from the AAPR Bulletin Today: Possible University of Tennessee job cuts will draw protest

Across the globe in New Zealand, the government will sign off on disbanding the country's Bioethics Council on Monday. The Bioethics Council was created in 2002 in response to public concern that the government was making decisions — in an ad hoc and unadvised manner — on complex and controversial biotech and genetic issues without considering the unique ethical, cultural and spiritual demographics of the country. Here is the story, from the Radio New Zealand newsfeed: Bioethics Council to be Disbanded

So what does this have to do with research ethics and ethics review boards? Well, plenty.

We should be concerned that the first cuts insitutions and governments want to make are on what they apparently consider to be highly expendable programs, like ethics. Seems to me that in perilous times, we just might need ethics a little more.

Ethics review boards, in either academic or medical settings, should be doing more than reviewing protocols, providing approvals and monitoring ongoing research in a silo somewhere, unconcerned that these kinds of cuts, as they don't name "research ethics" explicitly, have nothing to do with them. While reviewing research takes up a tremendous amount of time and energy, as I well know chairing an ethics review board myself, there is a certain amount of advocacy, outreach and education that an ethics review board must be committed to doing, on an ongoing and iterative basis.

So a few words on each of the three things I've identified here that ethics review boards should be committed to doing:

Advocacy for what? For strong ethics programs that are ideologically and financially supported by the administrators of the institution, situated logically within broader programs that have a commitment to research ethics; for fair, transparent and ethical processes in any context; and for fair treatment of not only participants — yes, that is our mandate — but also novice and experienced researchers, ethics review board members and others involved in research processes without whom researchers couldn't do their work. In these two cases, I would hope that those involved in research ethics at the University of Tennessee and from across NZ would speak out against the discontinuation of these broader ethics programs.

Outreach? Yes, outreach. Ethics review board members can do a great deal of outreach in their own departments and schools by articulating and clarifying what it is an ethics review board does, the kinds of principles upon which we base our deliberations and decisions, the challenges as well as the kinds of rewards that this work affords those who are dedicated to it and the kinds of broader values that ethics review boards, at their best, should be committed to upholding — things like autonomy of persons, voluntariness, maintaining dignity and integrity of persons and facilitating ethically sound research.

Outreach also implies making strong connections between ethics review boards, bioethicists and clinical ethicists, educators and other persons and programs within and between institutions.

Finally, education. As ethics review board members and those who are committed to research ethics in perhaps other ways, it's important, perhaps imperative, that we educate people not only about "what it is we do" but also why it's important to have people, who are concerned with ethics, hanging around. Bioethicists, clinical ethicists, research ethicists, those concerned with environmental ethics, business ethics...the list goes on. Usually most institutions don't think a great deal about these kinds of programs — and the associated dedicated people — until something goes wrong and suddenly, the institution turns to the same programs and people for help, advice and guidance. Seems that UT and NZ might not have anywhere to turn soon.

Condoms and ethics

This may be a bit of a stretch to highlight here, but honestly, I just wanted an excuse to blog about this. It's a fascinating study and one that, even just briefly covered in a national newspaper, spawned an outpouring of visceral and knee-jerk reactions.

Here is the very brief story from Wednesday's Globe and Mail: Condoms wanted; Experienced rubbers preferred

This story highlights a University of Windsor nursing research study in which, from what I can gather, participants will be asked to submit three months worth of their used condoms along with any that they might have been carrying around in their wallets or pockets (or anywhere else one might carry condoms). The researchers are essentially looking for microscopic holes in condoms (which are certainly a serious issue) caused by failures in use, storage and manipulation.

What's most interesting about this study is the flurry of comments from the public on, primarily, three things: The methodology, the fact that this research is (they assume) funded and the compensation for dropping off one's used condoms — fifty Canadian dollars.

Obviously, this study was approved by an ethics review board. And clearly, from only a cursory column in a newspaper, there is little one can realistically say about methodology or funding. There simply isn't enough information to comment on those two issues. But the compensation issue is a good one — and one that comes up, time and time again, in ethics review board discussions.

In this case, a few lay commentators were appalled at the amount of compensation for three months worth of used and unused condoms. Fifty dollars seems fairly reasonable to me, given the fact that participants will have to, well, gather up their used condoms at probably fairly inconvenient moments and put them delicately aside to provide for researchers. The collection of condoms will occur over three months for a total of 20 collected condoms — 10 used and 10 unused. One commentator stated that the amount of compensation would likely lead to an inducement of struggling university and college students to participate. While I'm not sure that fifty dollars would induce (as opposed to simply compensate) someone for their participation over three months, collecting what one needs to collect here, it's always worth asking a few important questions when looking at the amount of compensation offered in any research study:

1. What are participants being asked to do? How much time are they taking away from their own lives to participate in the study? What kind of burden are they assuming by being a participant?

2. Are basic costs of participating being covered? (Transportation or parking, child care if required, time away from work, time and effort)

2. Who are the participants? How much might their time be worth in another context? Would the amount offered be considerably more than they might get otherwise for a similar amount of time and effort?

3. How much is too much compensation?

4. When does compensation instead become inducement for participation in this study with these potential participants?

Offering first year University students, living on student loans, an iPod for one hour of their time to answer a survey would certainly, in most cases, count as undue inducement, enticing participation. Participants should be compensated not just for the costs that they endure in order to take part in the study, but also for their time, efforts, unique expertise in some cases and their usually altruistic willingness to participate in human research. However, it does require efforts on behalf of ethics review boards to decide, using common sense and attention to context, whether funds offered are in fact compensation or inducement. It's not always straightforward.

Thanks to AL for the story!

Harvard Med School Students Push for Stricter Conflict of Interest Policy

We blogged an earlier version of this story back in November: Research, Teaching, and Conflict of Interest. It was a story about a student-led movement go get Harvard Med School to tighten up its conflict of interest policy.

It was a student story in a student paper, back then. Now, it's hitting the big leagues.

The latest version is here, from the New York Times: Harvard Medical School in Ethics Quandary.

In a first-year pharmacology class at Harvard Medical School, Matt Zerden grew wary as the professor promoted the benefits of cholesterol drugs and seemed to belittle a student who asked about side effects.

Mr. Zerden later discovered something by searching online that he began sharing with his classmates. The professor was not only a full-time member of the Harvard Medical faculty, but a paid consultant to 10 drug companies, including five makers of cholesterol treatments.

Knowing that the revision of Harvard's COI policy is something students are pushing for is heartening; it's great seeing young professionals recognizing, and reacting to, a threat to the integrity of their profession. Of course, knowing that it's not faculty that are pushing for change is equally disheartening.

Relevant Books:
White Coat: Becoming A Doctor At Harvard Medical School, by Ellen Rothman.
Ethics and the University, by Michael Davis
Conflict of Interest in American Public Life, by Andrew Stark

Most Ethics Boards Permit Docs "Finder's Fees"

From the American Medical Association's American Medical News: Most IRB rules don't ban finder's fees for clinical trials

The American Medical Association, the American College of Physicians and others have declared unethical the practice of paying doctors "finder's fees" for recruiting patients as clinical research subjects. But only half of institutional review boards address in writing the conflict of interest these kinds of payment incentives pose, according to a survey of IRB policies at 117 medical schools that received National Institutes of Health research funding.

Interestingly, many ethics review boards don't explicitly ask about these kinds of (very common) finder's fees. Most ethics review forms and processes inquire about potential "conflicts of interest" as well as inclusion and exclusion criteria, but one can easily see how a researcher might make a plausible case that a finder's fee, per se, doesn't fit in any of the above categories. Some might say, well, it's not a conflict of interest, it's a fee for the time and energy it takes to screen, consent, collect data and follow up with participants. Furthermore, most ethics review forms simply ask for researchers to list inclusion and exclusion criteria. These kinds of fees aren't part of an inclusion criteria — they relate to the researcher, not the participants' characteristics. Finder's fees are clearly the result of a patient meeting the inclusion criteria and providing consent. This then means that these fees create a situation of conflict of interest. Remember, a COI is just a situation where someone (the clinical researcher in this case) is expected to exercise judgment on behalf of others, and has some "other" interest (e.g., getting a finder's fee) that stands to bias his or her judgment.

It's not all about physician-researchers either. Most large clinical studies employ research assistants or research nurses to manage the study by finding patients who are eligible, carrying out the consent process, collecting data and following up with patient participants. These research assistants often get a finder's fee (perhaps a hundred dollars per patient) in addition to their usually fairly modest salaries...

Ethics review boards take care to advise researchers about separating the recruitment phase from the consent phase of a study. This is done in order to allow persons who meet the inclusion criteria for a study to consider their potential participation and avoid the undue pressure or coercion that might be part of a too-quick process. They also take care to, in some kinds of research, ensure that the person recruiting and taking consent is not someone who is, for example, in a position of power over the potential participant — like their boss or professor, for example. These kinds of recommendations are made by ethics review boards in order to protect participants from things like coercion, undue influence or pressure to participate in a study. In other words, these strategies protect the voluntary nature of participation at the very vulnerable points of first contact, recruitment and consent.

If these kinds of strategies are being highly recommended by most conscientious ethics review boards, why would we also not have an explicit question on every ethics review form about whether or not money will be paid per participant successfully enrolled? It seems straightforward to me, as money is much more likely to influence the voluntariness of the recruitment and consent phases by perhaps making researchers (even unconsciously) apply pressure to participate, downplay risk or burden, overemphasize potential benefits or use techniques to convince people to sign up for the study. All the strategies I've outlined above, for protecting participants' right to participate voluntarily, are much less meaningful when there's money — for participation — on the line.

For more on the original study, see IRB: Ethics & Human Research Jan/Feb 2009 issue
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NOTE: due to a technical error, this posting shows up as having been authored by Chris MacDonald. It was in fact authored by Nancy Walton.

Why We Do Randomized, Double-Blind Trials

From yesterday's Business Ethics Blog: Fake Cures, Witch Doctors, and "Evidence"

What such companies and their customers need to learn about is the limits of personal testimonials. There are good reasons why drug companies are forced to do randomized, double-blind, clinical trials. To understand better, you just need to take a peek at the enormous literature on cognitive bias, which details the enormous number of ways in which first-person testimony can go awry. People have a tendency to see correlations, and even causes, where none exist. They tend to mis-estimate relevant probabilities. They tend to mis-remember key events. Reputable companies test their products in ways that minimize those effects.

Ethical concerns with evolving brain technologies

In the most recent issue of Nature, Jens Clausen, from the Institute of Ethics and History in Medicine at the University of Tübingen, has written a commentary on the evolving science of brain-implantable devices. Machines that are implanted in the brain aren't entirely new, notes Clausen, having already been used for enhancing hearing through cochlear implants, for pre-surgical diagnosis and monitoring of patients with epilepsy and for control of devastating motor control symptoms of end-stage Parkinson's through a technique called Deep Brain Stimulation.

Here's the story: Man, machine and in between

Clausen's main point in this commentary is that while some of these new and evolving technologies are unfamiliar, pose high risks and have unknown long term effects, the ethical concerns with brain-implantable devices aren't new ones per se. The issues — risk and vulnerability — are the same kinds of concerns that arise in other kinds of high-risk medical research with unknown outcomes.

Who would these kinds of devices be tested on? Normally, new drugs and devices undergo trials on healthy subjects as a first step in testing. However, with the significant risk of known side effects from implanting a device into a healthy person's brain (operative risk, bleeding, swelling, infection, etc.), testing on healthy individuals seems questionable, even inappropriate. Testing on those who already have neurological issues seems even more problematic, as they not only have an increased vulnerability due to the fact that they may be seriously ill but also their brains' functioning and reactions may be more unpredictable, when faced with an implanted device. Long term effects of implanting a device in our most complex organ, are, at this point, completely unknown. While the risk is high, as Clausen notes, it is even higher due to the degree of unknown short and long term risks.

He does, however, note some ethical concerns with the use of brain-implantable devices that, arguably, are unique to this technology and are, really, important philosophical and value-based concerns about how we define normal, abnormal and deficient in terms of human functioning. There is a danger that with the development of this kind of science, we may be driving the problematic concept of what is considered to be "normal" even further. Cochlear implants, for example, are surrounded by controversy. Many activists in the deaf community take an opposing stand towards the supposed "normalization" of children with deafness by the use of these implants, as the implication clearly is that deafness is an aberrance and to not be able to hear is to not be able to lead a full and rewarding life. As the science of engineering and controlling brain functions through the use of implantable devices progresses, there are some who would certainly warn against the drive to use this kind of technology to further define those with "deficiencies" and push them towards a dangerous and narrow standard of what is considered to be "normal".

If, instead, we look not at fixing what might be defined as "deficiencies" but at the very real possibility of enhancing "normal" functioning by, for example, using brain-implants to help professionals track athletes run faster, musicians to hear greater ranges of tones or allow mathematicians to calculate faster, this raises other kinds of ethical questions. Who would set limits on the technology in this case? Who would pay for it? How would we allocate resources — towards those who are paralyzed and could use devices to walk or move limbs or towards those who could have more than optimal, maybe even super-human functioning? The Six Million Dollar Man and the Bionic Woman might not be that far off.

This isn't to say that we shouldn't pursue this exciting and potentially very beneficial technology. But the ethical controversies are in fact, not the same as they've ever been in other areas of health research. Before we can plunge headfirst into thinking about the practicalities of conducting research using brain-implantable devices, we need to have much more discussion and contemplation on fundamental questions about how and why the technology might be used and subsequent implications for a diverse society.

Lack of consent for research on infants' blood samples

A recent story out of Texas describes how, since 2002, the state has been keeping the blood samples from infants' routine heel prick tests, without consent from parents. By law, the heel pricks are required by the state for all newborn infants to test for a number of birth defects. Prior to 2002, the blood was kept for a period of time, then destroyed. The "de-identified" samples are now kept indefinitely, without parental consent, for medical research of all kinds.

Here is the story, from the Austin American Statesman:
Texans unknowingly donate children's blood to research

Since 1965, Texas law has required the screening of newborns for birth defects, and the state now checks for 27 different health conditions — ranging from a gene that can cause severe mental disability to sickle cell anemia. In 2002, the state health department's Birth Defects Epidemiology and Surveillance Branch asked that the blood be stored for research rather than discarded; the department's leadership agreed. It contracted with Texas A&M [University's School of Rural Public Health] in 2006 to store the samples because the agency did not have room to keep them indefinitely, according to a Nov. 15, 2006, health department memo.

The agency says in the memo that it did not need to change state law to store the blood samples because "the agency's position has been that health-related research that uses these bloodspots is consistent with this agency's overall mission." The same memo says the department considers the blood samples to be "state records," which state law allows agencies to store indefinitely.

There are a couple of important issues that this story highlights:

1. According to the story, the state does not have to inform parents about how the blood samples might be used. Parents, "if they are aware of the tests", can opt out for "religious reasons". It's not clear from the story whether parents might actually be unaware that the initial battery of tests are even done on their own children (as consent is not sought) or whether they might be unaware of the fact that the samples will be used for future research and kept indefinitely. Either way, "opt out" options are almost always problematic in most contexts, but especially in this case, as it seems parents might be unaware of the testing, the use and storage of the samples or their right to opt out in the first place.

2. There is a difference, which is poorly understood by many people, between two basic and fundamentally important concepts: de-identified data and anonymized data. With anonymized data, the link between the biological sample (the data) and the patient is broken. Therefore the sample can't be traced back to a particular person. However, with de-identified samples, while they aren't labeled with any kind of obviously identifying information — like a name or SIN number — the samples can certainly be traced back to their respective donors. The fact that, according to this story, these are "de-identified" samples then leads to two questions. Do researchers who have access to these samples then have an ethical obligation to go back and contact those who provided the sample if they find, say, important or even devastating health information or if they want further information? Wouldn't contact like this be much more easily received by those who unwittingly provided the samples if instead, there had been an original consent to use their infants' blood for research in the first place?

3. If we think a little more about the first two issues here, we come to the third, perhaps most obvious issue. These are de-identified samples, collected for routine, mandated tests that can be traced back to the infants from whom they were taken, being used in all sorts of health research (i.e. whatever the state deems to be important and viable, as the state considers the samples to be their "state records" and not either personal health information or biological material owned by the individual). Why not just simply and clearly inform parents that these tests are being done as per state health regulations and then provide them with an opportunity to consent to allow the state to keep the samples indefinitely for research purposes? By informing parents up front, it would actually facilitate the goals and aims of keeping traceable samples indefinitely for research purposes — people would be far more receptive to possible future contact from researchers if they actually knew about and had consented to provide the samples in the first place.